Carbonic acid derivatives



Patented Sept. 19, 1939 UNITED STATES CARBONIC ACID DERIVATIVES Karl Miescher, Riehen, and Hans Kaegi, Basel, Switzerland, assignors to the firm Society of Chemical Industry in Basle, Basel, Switzerland N Drawing. Application December 14, 1937, Se-

rial No. 179,784. In Switzerland December 24,

6 Claims.

It has been found that new carbonic acid derivatives of saturated and unsaturated hydroxyketones of the type of the androstane-ol-ones can be obtained by causing these hydroxy-ketones to react with reactive carbonic acid derivatives.

The expression reactive carbonic acid derivatives as above used is understood to include for example carbonic acid halides such as phosgene, halogen carbonic esters, urea halides, as well as 10 isocyanates. In the halogen carbonic esters of the above hydroxy-ketones obtainable by using carbonic acid halides the halogen can be replaced by other groups, if desired, for example, alcohols, amines, amino alcohols, basic amines and the like.

The new compounds are to be used in therapeutics.

The following examples illustrate the invention, the parts being by weight:-

Example 1 1.4 parts of M-androstene-B-one-l'l-ol are dissolved in 5 parts of chloroform and 2 parts of phosgene are introduced into this solution while 5 cooling well. After allowing the mixture to stand for several hours in the cold and at room'temperature the solvent and the phosgene in excess are evaporated in a vacuum and the residue is redissolved from isopropylether. The chlorocarbonic ester of the A -androstene-3-one-l7-ol forms brilliant prisms melting at l39-140 C. with decomposition.

Starting from trans-dehydroandrosterone, the chlorocarbonic ester of the A -androstene-l'l- 5 one-3-ol of melting point 126-127 C. can be obtained in similar manner.

Example 2 A solution of 0.35 part of A -androstene-3- 40 one-ll-ol-chlorocarbonic ester in 1 part of henzene is mixed with 0.05 part of methanol and then with 0.1 part of pyridine. When the reaction is complete the whole is poured into water and the benzene solution is separated. After evaporating the solvent there is obtained the A androstene 3 onel'l-ol-methyl carbonate which, when recrystallized from isopropylether, melts at 141.5-142.5 C.

The following esters of the carbonic acid can be produced in analogous manner:A -androstene-B-one-l'l-ol-ethyl-carbonate of melting point 142 0.; A -andr0stene-3-one-17-ol-npropyl-carbonate of melting point 87-88 (7.; A

androstene-3-one l'l ol phenyl-carbonate of melting point l44-145 C.; A -androstene-3-onel'l-ol-benzyl-carbonate of melting point 156- 157 C.

Example 3 A solution of 0.7 part of A -androstene-3-onel'l-ol-chloro-carbonate in 3 parts of benzene is mixed with a solution of 0.5 part of p-diethylamino-ethanol in 3 parts of benzene. After allowing the whole to stand for some time the reaction is complete. Water is then added to the m mixture and the benzene layer is separated. The latter is washed, dried and evaporated. The oily residue is dissolved in ether and mixed with etheral hydrochloric acid. The hydrochloride of the A -androstene-3-one-l'l-ol-fl-diethylamino- 15 ethyl-carbonate which has separated is recrystallized from acetone-isopropylether. It forms crystals which are very easily soluble in Water and melt at PIS- C.

Example 4 20 A solution of the A -androstene-3-one-17-01- chloro-carbonate in benzene is treated with an excess of ammonia gas. After washing the benzene solution is evaporated and the A -androstene-3-one-1'l-ol-carbaminate which is left is recrystallized from methyl alcohol. It forms crystals of melting point 160-161 C.

In analogous manner there is produced the A -androstene-3-one-l'l-ol-N-n-propyl-carbami mate of melting point -l91.5 C. when starting from A androstene 3 one-17-ol-chloro-carbonate and n-propylamine, and the A -androstene-l'l-one-3-ol-carbaminate of, melting point 207-208 C. when starting from A -androstene-17-one-3-ol-chloro-carbonate and am- 35 monia.

In similar manner there is also obtained for example testosterone 17 diethylamino ethyl carbaminate.

Example 5 40 C. as well as corresponding derivatives of the 4. The testosterone-17-a1ky1-carbonate. androstane-17-one-3-o1- or androstane-3-one- 5. Testosterone- 1'7 -diethylamino ethyl car 17-01. bonate, forming a hydrochloride of melting point What we claim is: 178-180 C.

1. The carbonic acid derivatives of saturated 6. Testosterone 17 -n-propy1- carbonate of 5 and unsaturated androstane-ol-ones. melting point 8788 C.

2. The carbonic acid derivatives of testosterone.

KARL MIESCHERQ 3. The chloro-carbonic ester of testosterone of HANS KAEGIl melting point139-140 C. 

